Metabolomic Changes after Subacute Exposure to Polycyclic Aromatic Hydrocarbons: A Natural Experiment among Healthy Travelers from Los Angeles to Beijing

Abstract

Emerging epidemiological evidence has associated exposure to polycyclic aromatic hydrocarbons (PAHs) with chronic diseases including cardiometabolic diseases and neurodegeneration. However, little information is available about their subacute effects, which may accumulate over years and contribute to chronic disease development. To fill this knowledge gap, we designed a natural experiment among 26 healthy young adults who were exposed to elevated PAHs for 10 weeks after traveling from Los Angeles to Beijing in 2014 and 2015. Serum was collected before, during, and after the trip for metabolomics analysis. We identified 50 metabolites that significantly changed 6–8 weeks after the travel to Beijing (FDR < 5%). The network analysis revealed two main independent modules. Module 1 was allocated to oxidative homeostasis-related response and module 2 to delayed enzymatic deinduction response. Remarkably, the module 1 metabolites were recovered 4–7 weeks after participants’ return, while the module 2 metabolites were not. Urinary hydroxylated PAHs were significantly associated with metabolites from both modules, while PAH carboxylic acids, likely metabolites of alkylated PAHs, were only associated with antioxidation-related metabolites. These results suggested differential subacute effects of unsubstituted and alkylated PAHs. Further studies are warranted to elucidate the role of the reversibility of metabolite changes in adverse health effects of PAHs.

Addressing Unresolved Complex Mixture of I/SVOCs Emitted From Incomplete Combustion of Solid Fuels by Nontarget Analysis

“…The alcohol/peroxide pathway can produce a less oxidized oxygenated organic aerosol (Z. Zhang et al., 2020). Additionally, polycyclic aromatic hydrocarbons (PAHs) induce negative impacts during gene expression via entry into cells and production of either intermediate or final metabolites (Dey et al., 2021; X. Lu et al., 2021; Mehmood et al., 2020). The adverse effects of I/SVOCs on SOA production and human health depend on their chemical components.…”

Analysis of temporal metabolic rewiring for human respiratory syncytial virus infection by integrating metabolomics and proteomics

“…To identify metabolites that significantly changed over time and with different cell lines, a linear regression model was used (Eq. 1 ) (Dyar et al, 2018 ; Lu et al, 2021 ). During model construction, each metabolite signal was defined as a single output variable, and different time points and cell lines were defined as input variables.…”

A Systematic Review of Polycyclic Aromatic Hydrocarbon Derivatives: Occurrences, Levels, Biotransformation, Exposure Biomarkers, and Toxicity

“…In these studies, APAHs’ carboxylic acid metabolites, originating from hydroxylation and subsequent oxidation, have been utilized as biomarkers. Lin et al suggested urinary carboxylic acid metabolites as APAH exposure biomarkers, a proposition further substantiated through their correlation with antioxidation-related metabolites in a naturalistic study involving 26 healthy young adults exposed to increased levels of PAHs over a span of 10 weeks. , Another investigation on a panel study encompassing 120 participants corroborated the association between urinary phenanthrene-2-carboxylic acid levels and personal exposure to 2-methylphenanthrene, the potential applicability of urinary phenanthrene-2-carboxylic acid concentrations as a biomarker for methylated PAH exposure . Despite the substantial amount of in vivo and in vitro research confirming the increased toxicity of OPAHs and XPAHs compared to the parent PAHs, reports of their biomarkers are still limited.…”

“…For example, the urinary biotransformation metabolites of PAHs serve as the preferred exposure biomarkers for estimating their internal exposure levels . In prior research, the hydroxylated PAHs, for instance, 1-hydroxypyrene (1-OHP), 1-naphthol, and 2-naphthol, were commonly used as biomarkers for determining internal PAH exposure levels, and significant correlations between these levels and alterations in risk of cardiovascular diseases, respiratory diseases, and liver toxicity were observed. − In addition, biotransformation is also crucial in determining the toxicity of both PAHs and PAH derivatives. It is widely recognized that PAHs themselves are biologically inactive, and their carcinogenic effects require metabolic activation to produce reactive intermediates, including diol-epoxides and o -quinones.…”